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MICA

Official Full Name
Homo sapiens MHC class I polypeptide-related sequence A DNA.
Background
MICA and MICB (Major Histocompatibility Complex class I Chain-related gene A and gene B) bind to the activating immunoreceptor NKG2D. NKG2D is expressed on NK (Natural Killer) cells, NKT cells, ??T cells and CD8+??T cells. Recognition of MICA and MICB by
Synonyms
MICA; MHC class I polypeptide-related sequence A; PERB11.1; HLA class I antigen; stress inducible class I homolog; MHC class I chain-related protein A; MIC-A; FLJ36918; FLJ60820; MGC21250; MGC111087

Brief Introduction

MICA is a tumor-related gene located on the short arm of human chromosome 6 with ectensive polymorphism. MICA gene contains 6 exons, exon 1 encodes L-precursor peptide, exon 2-4 encode extracellular alpha 1, alpha 2 and alpha 3 domains, exon 5 encodes transmembrane (TM) region, and exon 6 encodes cytoplasmic region.

The MICA gene is highly polymorphic. Up to now, more than 70 MICA alleles have been identified and numbered from MICA*001-MICA*065. Exons encoding the extracellular domain are the concentrated regions of the MICA allele polymorphism. In addition, there is a microsatellite polypeptide site (GCT) in the transmembrane region with a trinucleotide repeat sequence. According to the difference of GCT, they are named A4, A5, A5.1, A6, A7, A8 and A9. A5.1 inserts a G on the basis of A5, resulting in early termination in the transmembrane region.

In recent years, MICA has been found to be a ligand of NKG2D, which can significantly activate NK cells and T cells, so it plays an important role in anti-infective and anti-tumor immunity.

MICA Gene and Cancer

It was found that the MICA-A5.1 allele may be closely related to the occurrence of esophageal cancer and is a susceptible marker for esophageal cancer.

Studies have found that the occurrence and development of colorectal cancer is related to the polymorphism of MICA gene. It is speculated that the possible pathogenesis is due to the low affinity between the protein molecules encoded by certain types of MICA and NKG2D receptor genes on NK cells and CD8+ T cells, which results in the inability of these immune cells to activate effectively and the inability to perform normal immune surveillance function on tumor cells.

Studies have found that the frequency of MICA* 008: 01 in breast cancer patients is lower than that in normal persons. The possible reason is that the polymorphism of MICA gene makes the activation of NK cells different.

Five allele fragments including A4 (179 bp), A5 (182 bp), A5.1 (183 bp), A6 (185 bp) and A 9 (194 bp) have been found in exon 5 of MICA gene. Among them, A5.1 inserts a base G on the basis of A5, resulting in code-shift mutation. The microsatellite polymorphism in exon 5 is associated with autoimmune diseases such as head and neck squamous cell carcinoma, breast cancer, and diabetes mellitus. MICA microsatellite polymorphisms are associated with some tumors and may be related to their linkage imbalance with classical HLA I and II loci. In addition, studies have shown that the microsatellite polymorphism in exon 5 exists racial differences among different populations.

References:

  1. Zheng Qingfeng, et al. Microsatellite Polymorphism of Exon 5 of MICA and Correlation Study of Esophageal Cancer [J]. Chinese Journal of Immunology, 2017, (5).
  2. Chen En, et al. MICA gene polymorphism and susceptibility to colorectal cancer [J]. Experimental and Laboratory Medicine, 2016, (5).
  3. Feng Zhizhi, et al. MICA gene polymorphism and breast cancer [J]. Chinese Journal of Blood Transfusion, 2016, (9).
  4. Guo Jiaquan, et al. Correlation between breast cancer and MICA gene polymorphism [J]. Laser Biology Journal, 2015, (2).

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